NM_032932.6:c.64C>A

Variant names:

• chr17-31391916-C-A
• rs1450492515
• NM_032932.6:c.64C>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_032932.6(RAB11FIP4):​c.64C>A​(p.Arg22Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,202,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R22C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: RAB11FIP4 NM_032932.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39
• Publications: 0 publications found

Genes affected

RAB11FIP4 (HGNC:30267): (RAB11 family interacting protein 4) The protein encoded by this gene interacts with RAB11 and is thought to be involved in bringing recycling endosome membranes to the cleavage furrow in late cytokinesis. Hypoxic conditions can lead to an upregulation of the encoded protein and enhance the metastatic potential of hepatocellular carcinoma. [provided by RefSeq, Oct 2016]

ENSG00000306303 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2648241).
• BS2: High AC in GnomAdExome4 at 14 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032932.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB11FIP4	NM_032932.6	MANE Select	c.64C>A	p.Arg22Ser	missense	Exon 1 of 15	NP_116321.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB11FIP4	ENST00000621161.5	TSL:1 MANE Select	c.64C>A	p.Arg22Ser	missense	Exon 1 of 15	ENSP00000482620.1	Q86YS3-1
	RAB11FIP4	ENST00000964368.1		c.64C>A	p.Arg22Ser	missense	Exon 1 of 15	ENSP00000634427.1
	ENSG00000306303	ENST00000816883.1		n.170+346G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.0000116 AC: 14 AN: 1202762 Hom.: 0 Cov.: 31 AF XY: 0.0000102 AC XY: 6 AN XY: 589606

African (AFR) AF: 0.00 AC: 0 AN: 24660

American (AMR) AF: 0.00 AC: 0 AN: 18790

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18850

East Asian (EAS) AF: 0.00 AC: 0 AN: 26130

South Asian (SAS) AF: 0.00 AC: 0 AN: 53594

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27782

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3346

European-Non Finnish (NFE) AF: 0.0000132 AC: 13 AN: 981636

Other (OTH) AF: 0.0000208 AC: 1 AN: 47974

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Pathogenic	26
DANN	Uncertain	0.97
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.79	T
M_CAP	Pathogenic	0.79	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.4
PrimateAI	Pathogenic	0.95	D
Sift4G	Uncertain	0.013	D
Polyphen		0.020	B
Vest4		0.27
MutPred		0.31		Gain of phosphorylation at R22 (P = 0.0201)
MVP		0.068
ClinPred		0.73	D
GERP RS		2.1
PromoterAI		0.039	Neutral
Varity_R		0.21
gMVP		0.71
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1450492515; hg19: chr17-29718934;